Negative Priming Effect on Organic Matter Mineralisation in NE Atlantic Slope Sediments

The priming effect (PE) is a complex phenomenon which describes a modification (acceleration or retardation) in the mineralisation rate of refractory organic matter (OM) following inputs of labile material. PEs are well-studied in terrestrial ecosystems owing to their potential importance in the evolution of soil carbon stocks but have been largely ignored in aquatic systems despite the fact that the prerequisite for their occurrence, i.e. the co-existence of labile and refractory OM, is also true for sediments. We conducted stable isotope tracer experiments in continental margin sediments from the NE Atlantic (550–950 m) to study PE occurrence and intensity in relation to labile OM input. Sediment slurries were treated with increasing quantities of the ¹³C-labelled diatom Thalassiosira rotula and PE was quantified after 7, 14 and 21 days. There was a stepwise effect of diatom quantity on its mineralisation although mineralisation efficiency dropped with increasing substrate amounts. The addition of diatomaceous OM yielded a negative PE (i.e. retardation of existing sediment OM mineralisation) at the end of the experiment regardless of diatom quantity. Negative PE is often the result of preferential utilisation of the newly deposited labile material by the microbial community (“preferential substrate utilization”, PSU) which is usually observed at excessive substrate additions. The fact that PSU and the associated negative PE occurred even at low substrate levels in this study could be attributed to limited amounts of OM subject to priming in our study area (∼0.2% organic carbon [OC]) which seems to be an exception among continental slopes (typically >0.5%OC). We postulate that PEs will normally be positive in continental slope sediments and that their intensity will be a direct function of sediment OC content. More experiments with varying supply of substrate targeting C-poor vs. C-rich sediments are needed to confirm these hypotheses.     

Regulation of myocardial function by histidine-rich, calcium-binding protein

Impaired sarcoplasmic reticulum (SR) Ca release has been suggested to contribute to the depressed cardiac function in heart failure. The release of Ca from the SR may be regulated by the ryanodine receptor, triadin, junctin, calsequestrin, and a histidine-rich, Ca-binding protein (HRC). We observed that the levels of HRC were reduced in animal models and human heart failure. To gain insight into the physiological function of HRC, we infected adult rat cardiac myocytes with a recombinant adenovirus that contains the full-length mouse HRC cDNA. Overexpression (1.7-fold) of HRC in adult rat cardiomyocytes was associated with increased SR Ca load (28%) but decreased SR Ca-induced Ca release (37%), resulting in impaired Ca cycling and depressed fractional shortening (36%) as well as depressed rates of shortening (38%) and relengthening (33%). Furthermore, the depressed basal contractile and Ca kinetic parameters in the HRC-infected myocytes remained significantly depressed even after maximal isoproterenol stimulation. Interestingly, HRC overexpresssion was accompanied by increased protein levels of junctin (1.4-fold) and triadin (1.8-fold), whereas the protein levels of ryanodine receptor, calsequestrin, phospholamban, and sarco(endo)plasmic reticulum Ca-ATPase remained unaltered. Collectively, these data indicate that alterations in expression levels of HRC are associated with impaired cardiac SR Ca homeostasis and contractile function.     

Engineered polymeric nanoparticles for receptor-targeted blockage of oxidized low density lipoprotein uptake and atherogenesis in macrophages

Strategies to prevent the uptake of modified low density lipoproteins (LDLs) by immune cells, a major trigger of inflammation and atherogenesis, are challenged by complex interfacial factors governing LDL receptor-mediated uptake. We examine a new approach based on a family of "nanoblockers", which are designed to examine the role of size, charge presentation, and architecture on inhibition of highly oxidized LDL (hoxLDL) uptake in macrophages. The nanoblockers are macromolecules containing mucic acid, lauryl chloride, and poly(ethylene glycol) that self-assemble into 15-20 nm nanoparticles. We report that the micellar configuration of the macromolecules and the combined display of anionic (carboxylate) groups in the hydrophobic region of the nanoblockers caused the most effective inhibition in the uptake of hoxLDL by IC21 macrophages. The nanoblockers primarily targeted SR-A and CD36, the major scavenger receptors and modulated the "atherogenic" phenotype of cells in terms of the degree of cytokine secretion, accumulation of cholesterol, and "foam cell" formation. These studies highlight the promise of synthetically engineered nanoblockers against oxidized LDL uptake.     

Comparative study of field and laboratory tests for the evaluation of aerobic capacity in soccer players

The purpose of this study was to evaluate the maximal oxygen uptake (Vo(2)max) values in soccer players as assessed by field and laboratory tests. Thirty-five elite young soccer players were studied (mean age 18.1 +/- 1.0 years, training duration 8.3 +/- 1.5 years) in the middle of the playing season. All subjects performed 2 maximal field tests: the Yo-Yo endurance test (T(1)) for the estimation of Vo(2)max according to normogram values, and the Yo-Yo intermittent endurance test (T(2)) using portable telemetric ergospirometry; as well as 2 maximal exercise tests on the treadmill with continuous (T(3)) and intermittent (T(4)) protocols. The estimated Vo(2)max values of the T(1) test (56.33 ml.kg(-1).min(-1)) were 10.5%, 11.4%, and 13.3% (p < or = 0.05) lower than those of the T(2) (62.96 ml.kg(-1).min(-1)), T(3) (63.59 ml.kg(-1).min(-1)) and T(4) (64.98 ml.kg(-1).min(-1)) tests, respectively. Significant differences were also found between the intermittent exercise protocols T(1) and T(3) (p < or = 0.001) and the continuous exercise protocols T(2) and T(4) (p < or = 0.001). There was a high degree of cross correlation between the Vo(2)max values of the 3 ergospirometric tests (T(2) versus T(3), r = 0.47, p < or = 0.005; T(2) versus T(4), r = 0.59, p < or = 0.001; T(3) versus T(4) r = 0.79, p < or = 0.001). It is necessary to use ergospirometry to accurately estimate aerobic capacity in soccer players. Nevertheless, the Yo-Yo field tests should be used by coaches because they are easy and helpful tools in the training program setting and for player follow-up during the playing season.     

Foraging traits of native predators determine their vulnerability to a toxic alien prey

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Crystal structure of rabbit muscle glycogen phosphorylase a in complex with a potential hypoglycaemic drug at 2.0 A resolution

CP320626 has been identified as a potent inhibitor, synergistic with glucose, of human liver glycogen phosphorylase a (LGPa), a possible target for type 2 diabetes therapy. CP320626 is also a potent inhibitor of human muscle GPa. In order to elucidate the structural basis of the mechanism of CP320626 inhibition, the structures of T state rabbit muscle GPa (MGPa) in complex with glucose and in complex with both glucose and CP320626 were determined at 2.0 A resolution, and refined to crystallographic R values of 0.179 (R(free)=0.218) and 0.207 (R(free)=0.235), respectively. CP320626 binds at the new allosteric site, some 33 A from the catalytic site, where glucose binds. The binding of CP320626 to MGPa does not promote extensive conformational changes except for small shifts of the side chain atoms of residues R60, V64, and K191. Both CP320626 and glucose promote the less active T state, while structural comparisons of MGPa-glucose-CP320626 complex with LGPa complexed with a related compound (CP403700) and a glucose analogue inhibitor indicate that the residues of the new allosteric site, conserved in the two isozymes, show no significant differences in their positions.     

Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment – a prospective, controlled study

The efficiency of activating latent transforming growth factor (TGF)-β₁ in systemic lupus erythematosus (SLE) may control the balance between inflammation and fibrosis, modulating the disease phenotype. To test this hypothesis we studied the ability to activate TGF-β₁ in SLE patients and control individuals within the context of inflammatory disease activity, cumulative organ damage and early atherosclerosis. An Activation Index (AI) for TGF-β₁ was determined for 32 patients with SLE and 33 age-matched and sex-matched control individuals by quantifying the increase in active TGF-β₁ under controlled standard conditions. Apoptosis in peripheral blood mononuclear cells was determined by fluorescence-activated cell sorting. Carotid artery intima-media thickness was measured using standard Doppler ultrasound. These measures were compared between patients and control individuals. In an analysis conducted in patients, we assessed the associations of these measures with SLE phenotype, including early atherosclerosis. Both intima-media thickness and TGF-β₁ AI for SLE patients were within the normal range. There was a significant inverse association between TGF-β₁ AI and levels of apoptosis in peripheral blood mononuclear cells after 24 hours in culture for both SLE patients and control individuals. Only in SLE patients was there a significant negative correlation between TGF-β₁ AI and low-density lipoprotein cholesterol (r = -0.404; P = 0.022) and between TGF-β₁ AI and carotid artery intima-media thickness (r = -0.587; P = 0.0004). A low AI was associated with irreversible damage (SLICC [Systemic Lupus International Collaborating Clinics] Damage Index ≥1) and was inversely correlated with disease duration. Intima-media thickness was significantly linked to total cholesterol (r = 0.371; P = 0.037). To conclude, in SLE low normal TGF-β₁ activation was linked with increased lymphocyte apoptosis, irreversible organ damage, disease duration, calculated low-density lipoprotein levels and increased carotid IMT, and may contribute to the development of early atherosclerosis.     

Cell death induced by GSM 900-MHz and DCS 1800-MHz mobile telephony radiation

In the present study, the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay--a well known technique widely used for detecting fragmented DNA in various types of cells--was used to detect cell death (DNA fragmentation) in a biological model, the early and mid stages of oogenesis of the insect Drosophila melanogaster. The flies were exposed in vivo to either GSM 900-MHz (Global System for Mobile telecommunications) or DCS 1800-MHz (Digital Cellular System) radiation from a common digital mobile phone, for few minutes per day during the first 6 days of their adult life. The exposure conditions were similar to those to which a mobile phone user is exposed, and were determined according to previous studies of ours [D.J. Panagopoulos, A. Karabarbounis, L.H. Margaritis, Effect of GSM 900-MHz mobile phone radiation on the reproductive capacity of D. melanogaster, Electromagn. Biol. Med. 23 (1) (2004) 29-43; D.J. Panagopoulos, N. Messini, A. Karabarbounis, A.L. Philippetis, L.H. Margaritis, Radio frequency electromagnetic radiation within "safety levels" alters the physiological function of insects, in: P. Kostarakis, P. Stavroulakis (Eds.), Proceedings of the Millennium International Workshop on Biological Effects of Electromagnetic Fields, Heraklion, Crete, Greece, October 17-20, 2000, pp. 169-175, ISBN: 960-86733-0-5; D.J. Panagopoulos, L.H. Margaritis, Effects of electromagnetic fields on the reproductive capacity of D. melanogaster, in: P. Stavroulakis (Ed.), Biological Effects of Electromagnetic Fields, Springer, 2003, pp. 545-578], which had shown a large decrease in the oviposition of the same insect caused by GSM radiation. Our present results suggest that the decrease in oviposition previously reported, is due to degeneration of large numbers of egg chambers after DNA fragmentation of their constituent cells, induced by both types of mobile telephony radiation. Induced cell death is recorded for the first time, in all types of cells constituting an egg chamber (follicle cells, nurse cells and the oocyte) and in all stages of the early and mid-oogenesis, from germarium to stage 10, during which programmed cell death does not physiologically occur. Germarium and stages 7-8 were found to be the most sensitive developmental stages also in response to electromagnetic stress induced by the GSM and DCS fields and, moreover, germarium was found to be even more sensitive than stages 7-8.     

Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs

Acyl ureas were discovered as a novel class of inhibitors for glycogen phosphorylase, a molecular target to control hyperglycemia in type 2 diabetics. This series is exemplified by 6-{2,6-Dichloro- 4-[3-(2-chloro-benzoyl)-ureido]-phenoxy}-hexanoic acid, which inhibits human liver glycogen phosphorylase a with an IC(50) of 2.0 microM. Here we analyze four crystal structures of acyl urea derivatives in complex with rabbit muscle glycogen phosphorylase b to elucidate the mechanism of inhibition of these inhibitors. The structures were determined and refined to 2.26 Angstroms resolution and demonstrate that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Acyl ureas induce conformational changes in the vicinity of the allosteric site. Our findings suggest that acyl ureas inhibit glycogen phosphorylase by direct inhibition of AMP binding and by indirect inhibition of substrate binding through stabilization of the T' state.